Using the isolated perfused rat hindquarter, I plan to: 1) assess the effects of experimental uremia on rat skeletal muscle release of amino acids, and protein synthesis and degradation; 2) determine the effects of alpha-deto-isocaproate, the keto-analogue of leucine, on rat skeletal muscle amino acid release and protein synthesis and degradation in normal and uremic rats; and 3) to determine the effects in uremic rats of a diet based on essential amino acids and/or their nitrogen-free analogues on free intracellular amino acids in muscle and on protein turnover of muscle. In rats made uremic by intragastric re-infusion of a constant percentage of excreted urine, I plan to develop a nutritional formulation for continuous administration that is designed to minimize the rate of excretion of catabolic products and to assess the efficacy of this formulation in three ways: 1) the ability of this formulation to sustain growth at levels of renal impairment at which growth is not achieved by conventional diets; 2) its ability to prevent secondary hyperparathyroidism; and 3) its ability to prevent the progressive loss of renal function that occurs in the cauterized remnant kidney.